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​Targeting Palmitic Acid Signaling Machinery to Inhibit Metastatic Cancer

Project description

Targeting lipid metabolism for metastasis treatment

The spread of cancer cells from a primary site to distant organs accounts for 90 % of cancer-related deaths and remains largely incurable. Emerging evidence highlights the critical role of lipids in metastasis, which provide energy, membrane components, and activate signalling pathways that drive tumour progression. Notably, palmitic acid uniquely promotes metastasis by inducing lipid metabolism reprogramming and epigenetic remodelling. Beyond fuelling cancer cells, fatty acids also regulate protein lipidation, a key process in metastasis. The ERC-funded PalmitoMET project aims to develop inhibitors that target this lipid signalling pathway to treat metastasis. These inhibitors could become first-in-class drugs with significant therapeutic potential against metastases.

Objective

Despite recent breakthroughs in immunotherapy and cancer research, metastasis continues to be responsible for 90% of cancer related deaths. While surgical resection and adjuvant therapy can cure localized tumors, once tumor cells metastasize, cancer remains largely incurable. Increasing evidence indicates that lipids play a crucial role in the metastatic process by providing energy and membrane components required for cell migration and outgrowth, and also by triggering specific signaling cascades that prime cancer cells into a metastatic program (Martin-Perez et al., Cell Metabolism 2022). Importantly, we have found that palmitic acid, but not other fatty acids, promotes metastasis in a large number of tumors, and that metastatic initiating cells require a lipid metabolism reprogramming driven by an epigenetic remodeling (Pascual et al. Nature 2017; Pascual et al. Nature 2021). We have solid evidence that fatty acids not only promote metastasis by providing energy to metastatic cells (Delauney et al. Nature 2022), but also by specifically modulating protein lipidation. Thus, targeting this particular lipid signaling machinery may represent an unexplored solution to combat metastasis. PalmitoMET aims to identify novel molecules capable of inhibiting specific protein lipidation to treat metastasis in preclinical models, with the aim to bring them closer to the clinic. Inhibitors found during this project have the potential to become first-in-class drugs, making this project a high risk but high gain project, considering the very large and growing market we are addressing

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2023-POC

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Host institution

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
08028 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

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